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Comparison of imipenem/cilastatin (I/C) and meropenem (M) attainment of pharmacodynamic (PD) target goals at various dosage regimens using a short (30‐min) infusion time
Author(s) -
Lee L. S.,
Lee L. S.,
Bertino J. S.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.053
Subject(s) - meropenem , imipenem/cilastatin , cilastatin , pharmacodynamics , imipenem , pharmacology , medicine , pharmacokinetics , anesthesia , chemistry , antibiotics , antibiotic resistance , biochemistry
I/C and M are 2 carbapenems with a broad spectrum of antimicrobial activity. There are few comparative data on attainment of PD target goals (time of free drug concentration above the minimum inhibitory concentration or T>MIC) by these agents at dosage regimens used clinically. T>MIC of 40% is considered a minimal PD target for efficacy. WinNonlin ® 3.1 was used to simulate the pharmacokinetics of I/C and M at various doses and dosing intervals infused over the labeled infusion time of 30‐min and assess T>MIC for each regimen. A 2‐compartment IV infusion model was used utilizing published population pharmacokinetic values. T>MIC was evaluated using MICs of 1, 2, and 4 (interpreted as susceptible organisms), 8 ( intermediate susceptibility ), and 16 ( resistant organisms) μg/mL. Mann‐Whitney rank sum test was used to compare the %T>MIC for I/C and M at each regimen. A p value of <0.05 was significant.(See Table) Clinical Pharmacology & Therapeutics (2004) 75 , P14–P14; doi: 10.1016/j.clpt.2003.11.053Drug and Dosage Free Drug %T>MIC for each MIC (T>MIC≥40% bolded ) 1 2 4 8 16I/C 250mg Q6H 62.5 45.8 29.2 15 0 M 250mg Q6H 45.8 31.2 21.7 18.3 0 I/C 500mg Q6H 79.2 62.5 45.8 29.2 12.5 M 500mg Q6H 62.5 45.8 29.2 21 12.5 I/C 500mg Q8H 59.4 45 32.5 20 11.8 M 500mg Q8H 49.3 34.3 21.8 15.6 9.3 I/C 1000mg Q6H 100 79.2 60 45.8 29.2 M 1000mg Q6H 79.2 62.5 45.8 31.7 21 I/C 1000mg Q8H 71.8 59.4 46.9 34.3 21.9 M 1000mg Q8H 59.4 46.8 34.4 21.9 15.6No significant differences were noted between I/C and M in T>MIC. For some MICs, the T>MIC for I/C was>40% whereas that for M was not. Decisions on the selection of these agents should be based on potential toxicities and cost since comparative regimens attain similar PD targets.